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Self-assembling human skeletal organoids for disease modeling and drug testing

Abraham, Diana M; Herman, Calvin; Witek, Lukasz; Cronstein, Bruce N; Flores, Roberto L; Coelho, Paulo G
Skeletal conditions represent a considerable challenge to health systems globally. Barriers to effective therapeutic development include a lack of accurate preclinical tissue and disease models. Most recently, work was attempted to present a novel whole organ approach to modeling human bone and cartilage tissues. These self-assembling skeletal organoids mimic the cellular milieu and extracellular organization present in native tissues. Bone organoids demonstrated osteogenesis and micro vessel formation, and cartilage organoids showed evidence of cartilage development and maturation. Skeletal organoids derived from both bone and cartilage tissues yielded spontaneous polarization of their cartilaginous and bone components. Using these hybrid skeletal organoids, we successfully generated "mini joint" cultures, which we used to model inflammatory disease and test Adenosine (A2A ) receptor agonists as a therapeutic agent. The work and respective results indicated that skeletal organoids can be an effective biological model for tissue development and disease as well as to test therapeutic agents.
PMID: 34837719
ISSN: 1552-4981
CID: 5063982

Effects of a local single dose administration of growth hormone on the osseointegration of titanium implants

Grossi, J-R; Parra, M; Benalcázar-Jalkh, E-B; Giovanini, A-F; Zielak, J-C; Sebstiani, A-M; Gonzaga, C-C; Coelho, P-G; Witek, L; Deliberador, T-M
BACKGROUND:The aim of the present study was to evaluate the effect of different concentrations of growth hormone (GH) on endosteal implant's surface at the early stages of osseointegration. MATERIAL AND METHODS/METHODS:Sixty tapered acid-etched titanium implants were divided into four groups: i) Collagen, used as a control group; and three experimental groups, where after collagen coating, GH was administered directly to the surface in varying concentrations: ii) 0.265 mg, iii) 0.53 mg, and iv) 1 mg. Implants were placed in an interpolated fashion in the anterior flange of C3, C4 or C5 of 15 sheep with minimum distance of 6 mm between implants. After 3-, 6- and 12-weeks of healing samples were harvested, histologically processed, qualitatively and quantitatively assessed for bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO). RESULTS:Statistical analysis as a function of time in vivo and coating resulted in no significant differences for BIC and BAFO at any evaluation time point. Histological evaluation demonstrated similar osseointegration features for all groups with woven bone formation at 3 weeks and progressive replacement of woven for lamellar bone in close contact with the implant surface and within the implant's threads. CONCLUSIONS:A single local application of growth hormone to the surface of titanium implants did not yield improved implant osseointegration independent of healing time.
PMID: 35218646
ISSN: 1698-6946
CID: 5172642

Osteoradionecrosis following radiation to reconstructed mandible with titanium plate and osseointegrated dental implants

Byun, David J; Daar, David A; Spuhler, Karl; Anzai, Lavinia; Witek, Lukasz; Barbee, David; Jacobson, Adam S; Levine, Jamie P; Hu, Kenneth S
PMID: 34706296
ISSN: 1879-8519
CID: 5042562

Effects of local single dose administration of parathormone on the early stages of osseointegration: A pre-clinical study

Grossi, João Ricardo Almeida; Deliberador, Tatiana Miranda; Giovanini, Allan Fernando; Zielak, João César; Sebstiani, Aline Monise; Gonzaga, Carla Castiglia; Coelho, Paulo G; Zétola, André Luis; Weiss, Fernando P; Benalcázar Jalkh, Ernesto B; Storrer, Carmen Lucia Mueller; Witek, Lukasz
The present study aimed to evaluate the effect of parathormone (PTH) administered directly to the implant's surface prior to insertion, using a large translational animal model. Sixty titanium implants were divided into four groups: (i) Collagen, control group, where implants were coated with Type-I Bovine-collagen, and three experimental groups, where implants received varying doses of PTH: (ii) 12.5, (iii) 25, and (iv) 50 μg, prior to placement. Fifteen female sheep (~2 years old, weighing ~65 kg) received four implants in an interpolated fashion in C3, C4 or C5 vertebral bodies. After 3-, 6- and 12-weeks, samples were harvested, histologically processed, qualitatively and quantitatively assessed for bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO). BIC yielded lower values at 6-weeks for 50 μg relative to the control group, with no significant differences, when compared to the 12.5- and 25-μg. No significant differences were detected at 6-weeks between collagen, 12.5- and 25-μg groups. At 3- and 12-weeks, no differences were detected for BIC among PTH groups. With respect to BAFO, no significant differences were observed between the control and experimental groups independent of PTH concentration and time in vivo. Qualitative observations at 3-weeks indicated the presence of a more mature bone near the implant's surface with the application of PTH, however, no significant differences in new bone formation or healing patterns were observed at 6- and 12-weeks. Single local application of different concentrations of PTH on titanium implant's surface did not influence the osseointegration at any time-point evaluation in low-density bone.
PMID: 35218605
ISSN: 1552-4981
CID: 5172632

3D-printed resins for provisional dental restorations: Comparison of mechanical and biological properties

Atria, Pablo J; Bordin, Dimorvan; Marti, Felipe; Nayak, Vasudev Vivekanand; Conejo, Julian; Benalcázar Jalkh, Ernesto; Witek, Lukasz; Sampaio, Camila S
OBJECTIVES/OBJECTIVE:To characterize the mechanical and biological properties of three commercially available resins, which are currently used for provisional restorations and to compare them to an experimental resin intended for definitive fixed dental prostheses. MATERIALS AND METHODS/METHODS:Three commercially available resins: Crowntec (CT, Saremco), Temporary C&B (FL, Formlabs), C&B MFH (ND, Nextdent), and the experimental resin: Permanent Bridge (PB, Saremco) were printed and subjected to biaxial flexural strength test, finite element analysis, Weibull analysis, scanning electron microscopy, cell proliferation, immunohistochemistry and cytotoxicity assays. Samples from CT, PB, and ND were provided directly from the manufacturers ensuring ideal workflow. FL was printed using the workflow as recommended by the manufacturer, using a Formlabs 2 printer and their post-processing units Form Wash and Form Cure. RESULTS:From the tested resins, PB yielded the best overall results in terms of mechanical properties. Cell proliferation and cytotoxicity did not show any significant differences among materials. PB showed higher values for probability of survival predictions (35%) when subjected to 250 MPa loads, whereas the other materials did not reach 10%. SIGNIFICANCE/CONCLUSIONS:Despite mechanical differences between the evaluated materials, the outcomes suggest that 3D printed provisional resins may be used in clinical settings, following the manufacturers indications. New materials intended for long-term use, such as the PB resin, yielded higher mechanical properties compared to the other materials. Alternative printing and post-processing methods have not yet been evaluated and should be avoided until further literature is available. CLINICAL SIGNIFICANCE/CONCLUSIONS:3D printed resins for provisional restorations have become popular with the emergence of new technologies. In this study, we evaluated three different commercially available resins for provisional restorations and one new experimental resin. The results from this study indicate that commercially available resins could be used in clinical settings under certain conditions and limited periods of time. Following the manufacturers protocols is of paramount importance to not compromise these properties.
PMID: 35187786
ISSN: 1708-8240
CID: 5167732

Physiochemical and bactericidal activity evaluation: Silver-augmented 3D-printed scaffolds-An in vitro study

Nayak, Vasudev Vivekanand; Tovar, Nick; Hacquebord, Jacques Henri; Duarte, Simone; Panariello, Beatriz H D; Tonon, Caroline; Atria, Pablo J; Coelho, Paulo G; Witek, Lukasz
HYPOTHESIS/OBJECTIVE:Injuries requiring resection of tissue followed by autogenous bone transfer may be prone to infection by Staphylococcus aureus, impeding recovery and increasing medical costs. For critical sized defects, the common approach to reconstruction is a tissue transfer procedure but is subject to limitations (e.g., donor site morbidity, cost, operating time). Utilizing beta tricalcium phosphate (β-TCP) as bone grafting material augmented with silver (Ag), a custom graft may be 3D printed to overcome limitations and minimize potential infections. EXPERIMENTS/METHODS:) groups followed by electron microscopy, thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) to gather information of chemical and physical properties. Preliminary biocompatibility and bactericidal capacity of the scaffolds were tested using human osteoprogenitor (hOP) cells and methicillin-sensitive S. aureus strain, respectively. RESULTS:groups, whereas electron microscopy showed a decrease in Ca and an increase in Ag ions, decreasing Ca/P ratio with increasing surfactant concentrations. PrestoBlue assays yielded an increase in fluorescence cell counts among experimental groups with lower concentrations of Ag characterized by their characteristic trapezoidal shape whereas cytotoxicity was observed at higher concentrations. Similar observations were made with alkaline phosphatase assays. Antimicrobial evaluation showed reduced colony-forming units (CFU) among all experimental groups when compared to 100% β-TCP. β-TCP scaffolds augmented with Ag ions facilitate antibacterial effects while promoting osteoblast adhesion and proliferation.
PMID: 34196107
ISSN: 1552-4981
CID: 4932082

Effects of a local single dose administration of growth hormone on the osseointegration of titanium implants

Almeida Grossi, Joao Ricardo; Parra, Marcelo; Benalcazar-Jalkh, Ernesto B.; Giovanini, Allan Fernando; Zielak, Joao Cesar; Sebstiani, Aline Monise; Gonzaga, Carla Castiglia; Coelho, Paulo G.; Witek, Lukasz; Deliberador, Tatiana Miranda
ISSN: 1698-6946
CID: 5182812

Effects of local single dose administration of parathormone on the early stages of osseointegration: A pre-clinical study

Almeida Grossi, Joao Ricardo; Deliberador, Tatiana Miranda; Giovanini, Allan Fernando; Zielak, Joao Cesar; Sebstiani, Aline Monise; Gonzaga, Carla Castiglia; Coelho, Paulo G.; Zetola, Andre Luis; Weiss, Fernando P.; Benalcazar Jalkh, Ernesto B.; Mueller Storrer, Carmen Lucia; Witek, Lukasz
ISSN: 1552-4973
CID: 5182772

Tissue Engineering Strategies for Craniomaxillofacial Surgery: Current Trends in 3D-Printed Bioactive Ceramic Scaffolds

Chapter by: Witek, L; Nayak, V V; Runyan, C M; Tovar, N; Elhage, S; Melville, J C; Young, S; Kim, D H; Cronstein, B N; Flores, R L; Coelho, P G
in: Innovative Bioceramics in Translational Medicine II by Choi, Andy H; et al (Eds)
[S.l.] : Springer, 2022
pp. 55-74
ISBN: 9789811674389
CID: 5165022

Residual stress estimated by nanoindentation in pontics and abutments of veneered zirconia fixed dental prostheses

Fardin, Vinicius Pavesi; Bonfante, Gerson; Coelho, Paulo G; Bergamo, Edmara T P; Bordin, Dimorvan; Janal, Malvin N; Tovar, Nick; Witek, Lukasz; Bonfante, Estevam A
Glass ceramics' fractures in zirconia fixed dental prosthesis (FDP) remains a clinical challenge since it has higher fracture rates than the gold standard, metal ceramic FDP. Nanoindentation has been shown a reliable tool to determine residual stress of ceramic systems, which can ultimately correlate to failure-proneness.
PMID: 35476114
ISSN: 1678-7765
CID: 5206382